Natural products have played a pivotal role in the discovery and development of modern chemotherapeutics. Thus, the genesis of more than 70% of all small molecule anti-cancer medicines approved in the last 70 years can be traced to natural products. Although the key role of natural products in drug discovery remains uncontested few of them have undergone comprehensive structure-activity relationship (SAR) studies and exhaustive bioactivity screenings. This is primarily due to the prevailing scarcity of the natural products compounded with limited options for structural modifications which are necessary for the SAR studies. Synthesis of these natural products offers the opportunity to access the natural product and its numerous congeners through changes in the synthetic strategy. Due to the limited number of reliable enantioselective catalytic reactions many syntheses rely on the elaboration of chiral starting materials along circuitous synthetic routes. This affects the efficiency and narrows flexibility and applicability of the syntheses. The 1,2-oxazine natural products have been particularly affected by this shortcoming. This is a serious limitation for the discovery of new chemotherapeutics since many of these natural products possess unique and exciting biological activities. We aim to make the 1,2-oxazine core readily accessible through rational design of a novel enantioselective and catalytic cyclization reaction. We will also develop a straightforward methodology for the conversion of the cyclization products to the 1,2-oxazine natural products and their structural analogs that are unattainable using currently available methods. This methodology will then be employed for the synthesis of two 1,2-oxazine natural products that possess unique anti-cancer activities. This approach is based on the unprecedented catalytic enantioselective cyclization reaction and is innovative because (a) it has the potential to combine the undisputed efficiency and practicality of a catalytic asymmetric method with the ready availability of both precursors; and (b) the asymmetric cyclization reaction will allow rapid access to a variety of structurally related natura products by way of simple structural editing. These studies will improve our understanding of their biological properties and will potentially provide new leads for anti-cancer drug discovery.